Environmental Tobacco Smoke Exposure and Survival Following Breast Cancer Free

Few studies (1–4) have examined whether environmental tobacco smoke (ETS) exposure increases the risk of mortality among women with breast cancer, and no studies to date have prospectively examined the impact of postdiagnosis changes in ETS exposure on mortality. This study examined whether ETS exposure was associated with long-term all-cause and breast cancer–specific mortality among a population-based sample of women.

Participants of the Long Island Breast Cancer Study Project (LIBCSP), a population-based cohort of women newly diagnosed with breast cancer, were interviewed shortly after diagnosis and again about 5 years later and now continue to be followed for vital status. Details of the LIBCSP have been published previously (2, 5). Institutional Review Board approval was obtained from of all participating institutions.

ETS exposure was determined via structured interviews (2). Women were asked to report whether any members of the household smoked in their presence, the relationship of the smoker, the participant's ages at first/last exposure, and any time periods the household member did not smoke. Duration of exposure was categorized as <15 years, ≥15 to <30 years, and ≥30 years of exposure. Recency of exposure was categorized as <5 years, ≥5 to <10 years, and ≥10 years.

Covariates assessed via questionnaire included age, menopausal status, annual household income, education, marital status, body mass index (BMI), physical activity, intake of alcoholic beverages, cigarette smoking, and treatment. Estrogen receptor status and nodal involvement were determined by medical record. Tumor size was obtained from the NY State Cancer Registry.

Vital status of the 1,508 women diagnosed with breast cancer was determined using the National Death Index. Follow-up for mortality occurred from the date of diagnosis in 1996 to 1997 until December 31, 2014 (median = 17.61 years). We identified 597 deaths; 234 were associated with breast cancer.

Using multivariable Cox proportional regression models, we estimated HR and 95% confidence intervals (CI) for the associations between at-diagnosis as well as at-/postdiagnosis changes in ETS exposure and mortality following breast cancer. Models restricted to women with invasive cancer only yielded similar results from those of all women; only the latter are shown. All analyses were conducted using IBM SPSS Statistics Version 22.0 (IBM Corp.).

In analyses of at-diagnosis ETS exposure, survival time began at the date of breast cancer diagnosis and ended on the date of death or, if alive, December 31, 2014. In analyses examining postdiagnosis ETS exposure, survival time began at the date of completion of the follow-up questionnaire and ended on the date of death or, if alive, December 31, 2014. Missing covariates were imputed in SPSS using 25 imputations with 1,000 iterations. The imputation models included age at diagnosis, menopausal status, income, education, marital status, BMI, physical activity, alcohol intake, smoking status, post-diagnosis ETS exposure, disease characteristics (stage, tumor size, nodal involvement estrogen receptor status), treatment (radiation, chemotherapy, and hormone therapies), and the outcome (the event indicator and the Nelson–Aalen cumulative hazard estimator).

Approximately 15% of women reported ETS exposure in the year before diagnosis and 14% reported current exposure at the follow-up questionnaire.

There was little or no association between current ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78–1.40) or breast cancer–specific (HR = 0.98; 95% CI, 0.63–1.52) mortality after adjustment for covariates (Table 1). Risk of mortality was slightly elevated for all-cause (HR = 1.17; 95% CI, 0.74–1.86) and breast cancer–specific (HR = 1.13; 95% CI, 0.57–2.27) mortality when we restricted the analyses to never smokers, although the corresponding estimates were imprecise.

Although no associations were observed among women with ongoing ETS exposure, HRs were elevated 81% (HR = 1.81; 95% CI, 0.87–3.74) for all-cause mortality and 89% (HR = 1.89; 95% CI, 0.68–5.24) for breast cancer–specific mortality among women who reported cessation in postdiagnosis ETS exposure up to the year before the follow-up assessment (Table 2).

Exposure to the constituents of tobacco smoke, either through active smoking or exposure to ETS, is hypothesized to influence breast cancer progression through several mechanisms, including directly by influencing cell proliferation and metastasis (6) and indirectly by disrupting the endocrine system (7). In addition, because up to 70% of tar in ETS is in the vapor phase, whereas all of the tar in direct smoking is in the particulate phase, ETS may be an important source of exposure to carcinogens as particulate smoke is cleared into the mouth and swallowed, but vapor phase constituents are inhaled and absorbed into the bloodstream and lymph system (8). Despite these hypothesized mechanisms, the few studies conducted to date (1–4), including the sufficiently powered study reported here, provide limited or no evidence of an association between ETS exposure and survival after breast cancer. Although we observed an elevated risk of mortality among women with postdiagnosis cessation of ETS exposure, we could not rule out chance and reverse causation as possible explanations.

No potential conflicts of interest were disclosed.

Conception and design: H. Parada Jr, M.D. Gammon

Development of methodology: H. Parada Jr, P.T. Bradshaw, L.S. Engel, M.D. Gammon

Acquisition of data (provided animals, acquired and managed patients, provided facilities, etc.): P.T. Bradshaw, S.L. Teitelbaum, A.I. Neugut, R.M. Santella, M.D. Gammon

Analysis and interpretation of data (e.g., statistical analysis, biostatistics, computational analysis): H. Parada Jr, P.T. Bradshaw, L.S. Engel, S.E. Steck, A.I. Neugut, M.D. Gammon

Writing, review, and/or revision of the manuscript: H. Parada Jr, P.T. Bradshaw, L.S. Engel, K. Conway, S.E. Steck, S.L. Teitelbaum, A.I. Neugut, R.M. Santella, M.D. Gammon

Administrative, technical, or material support (i.e., reporting or organizing data, constructing databases): M.D. Gammon

Study supervision: M.D. Gammon

The Long Island Breast Cancer Study Project was funded by the NCI and the National Institute of Environmental Health Sciences grants UO1CA/ES66572 and UO1CA66572 (awarded to M.D. Gammon). H. Parada Jr was supported by T32 ES007018 and R25 CA057726.

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